A 2 × 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: a protocol for the CLEAR clinical trial
Judy Martina Bradley,
Rohan Anand,
Brenda O’Neill,
Kathryn Ferguson,
Mike Clarke,
Mary Carroll,
James Chalmers,
Anthony De Soyza,
Jamie Duckers,
Adam T. Hill,
Michael R. Loebinger,
Fiona Copeland,
Evie Gardner,
Christina Campbell,
Ashley Agus,
Alistair McGuire,
Roisin Boyle,
Fionnuala McKinney,
Naomi Dickson,
Danny F. McAuley,
Stuart Elborn,
On behalf of the CLEAR study group
Affiliations
Judy Martina Bradley
Wellcome-Wolfson Institute For Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast
Rohan Anand
Wellcome-Wolfson Institute For Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast
Brenda O’Neill
Centre for Health and Rehabilitation Technologies (CHaRT), Institute of Nursing and Health Research, Ulster University
Kathryn Ferguson
Northern Ireland Clinical Research Network, Belfast Health and Social Care Trust
Mike Clarke
Northern Ireland Methodology Hub, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast
Mary Carroll
Southampton University Hospitals NHS Trust
James Chalmers
School of Medicine, University of Dundee
Anthony De Soyza
NIHR Biomedical research centre (BRC) for Aging, Institute of Cellular Medicine, Newcastle University
Jamie Duckers
Cardiff and Vale University Health Board, University Hospital Llandough
Adam T. Hill
Centre for Inflammation Research, University of Edinburgh
Michael R. Loebinger
Faculty of Medicine, National Heart and Lung Institute, Imperial College and Royal Brompton Hospital
Fiona Copeland
PCD Family Support Group, Ciliopathy Alliance
Evie Gardner
Northern Ireland Clinical Trials Unit, Belfast Health and Social Care Trust
Christina Campbell
Northern Ireland Clinical Trials Unit, Belfast Health and Social Care Trust
Ashley Agus
Northern Ireland Clinical Trials Unit, Belfast Health and Social Care Trust
Alistair McGuire
Department of Health Policy, London School of Economics and Political Science
Roisin Boyle
Northern Ireland Clinical Trials Unit, Belfast Health and Social Care Trust
Fionnuala McKinney
Northern Ireland Clinical Trials Unit, Belfast Health and Social Care Trust
Naomi Dickson
Northern Ireland Clinical Trials Unit, Belfast Health and Social Care Trust
Danny F. McAuley
Wellcome-Wolfson Institute For Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast
Stuart Elborn
Wellcome-Wolfson Institute For Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast
Abstract Background Current guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum removal as part of standard care. We hypothesise that mucoactive agents (HTS or carbocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care. Methods This is a 52-week, 2 × 2 factorial, randomized, open-label trial to determine the clinical effectiveness and cost effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care - the Clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care (CLEAR) trial. Patients will be randomised to (1) standard care and twice-daily nebulised HTS (6%), (2) standard care and carbocisteine (750 mg three times per day until visit 3, reducing to 750 mg twice per day), (3) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (4) standard care. The primary outcome is the mean number of exacerbations over 52 weeks. Key inclusion criteria are as follows: adults with a diagnosis of BE on computed tomography, BE as the primary respiratory diagnosis, and two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum. Discussion This trial’s pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigour in other areas of trial delivery. The CLEAR trial will provide evidence as to whether HTS, carbocisteine or both are effective and cost effective for patients with BE. Trial registration EudraCT number: 2017-000664-14 (first entered in the database on 20 October 2017). ISRCTN.com, ISRCTN89040295. Registered on 6 July/2018. Funder: National Institute for Health Research, Health Technology Assessment Programme (15/100/01). Sponsor: Belfast Health and Social Care Trust. Ethics Reference Number: 17/NE/0339. Protocol version: v3.0 Final_14052018.
